Scala e al. BMC Bioin o ma ics (2019) 20:79
h ps://doi.o g/10.1186/s12859-019-2639-2
SOFTWARE Open Access
FunMappOne: a ool o hie a chically
o ganize and isually na iga e unc ional gene
anno a ions in mul iple expe imen s
Gio anni Scala1,2,3, Angela Se a1,2, Vee Singh Ma wah1,2, Lau a Aliisa Saa imäki1,2 and Da io G eco1,2,3 *
Abs ac
Backg ound: Func ional anno a ion o genes is an essen ial s ep in omics da a analysis. Mul iple da abases and
me hods a e cu en ly a ailable o summa ize he unc ions o se s o genes in o highe le el ep esen a ions, such as
on ologies and molecula pa hways. Anno a ing esul s om omics expe imen s in o unc ional ca ego ies is essen ial
no only o unde s and he unde lying egula o y dynamics bu also o compa e mul iple expe imen al condi ions a
a highe le el o abs ac ion. Se e al ools a e al eady a ailable o he communi y o ep esen and compa e
unc ional p o iles o omics expe imen s. Howe e , when he numbe o expe imen s and/o en iched unc ional
e ms is high, i becomes di icul o in e p e he esul s e en when g aphically ep esen ed. The e o e, he e is
cu en ly a need o in e ac i e and use - iendly ools o g aphically na iga e and u he summa ize anno a ions in
o de o acili a e esul s in e p e a ion also when he dimensionali y is high.
Resul s: We de eloped an app oach ha exploi s he in insic hie a chical s uc u e o se e al unc ional anno a ions
o summa ize he esul s ob ained h ough en ichmen analyses o highe le els o in e p e a ion and o map gene
ela ed in o ma ion a each summa ized le el. We buil a use - iendly g aphical in e ace ha allows o isualize he
unc ional anno a ions o one o mul iple expe imen s a once. The ool is implemen ed as a R-Shiny applica ion
called FunMappOne and is a ailable a h ps://gi hub.com/g ecolab/FunMappOne.
Conclusion: FunMappOne is a R-shiny g aphical ool ha akes in inpu mul iple lis s o human o mouse genes,
op ionally along wi h hei ela ed modi ica ion magni udes, compu es he en iched anno a ions om Gene
On ology, Kyo o Encyclopedia o Genes and Genomes, o Reac ome da abases, and epo s in e ac i e maps o
unc ional e ms and pa hways o ganized in a ional g oups. FunMappOne allows a as and con enien compa ison
o mul iple expe imen s and an easy way o in e p e esul s.
Keywo ds: Func ional anno a ion, Pa hway isualiza ion, On ology isualiza ion, KEGG, Gene On ology, Reac ome,
R-Shiny
Backg ound
Func ional anno a ion o la ge se s o signi ican genes
is o en he inal s ep o omics da a analysis. Howe e ,
when mul iple genes a e selec ed du ing di e en ial anal-
ysis, i becomes almos impossible o unde s and he
al e ed biological p ocesses by manually inspec ing he
*Co espondence: [email p o ec ed]
1Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, A o Ylpön ka u
34 - A o building, FI-33014 Tampe e, Finland
2BioMediTech Ins i u e, Uni e si y o Tampe e, A o Ylpön ka u 34 - A o
building, FI-33014 Tampe e, Finland
Full lis o au ho in o ma ion is a ailable a he end o he a icle
indi idual genes. This ask is e en mo e di icul when
compa ing unc ional p o iles de i ed om wo o mo e
ela ed expe imen s a he gene le el, o di e en se s o
unc ionally ela ed genes may be speci ically a ec ed in
di e en expe imen al condi ions.
A mul i ude o ools a e al eady a ailable o he com-
muni y o g aphically ep esen en iched unc ional anno-
a ions om single pai -wise compa isons [1–4]. When
conside ing mul iple expe imen s, hese me hods equi e
o un sepa a e analyses o each expe imen and subse-
quen ly colla e he esul s o compa ison. The complexi y
o his ask inc eases wi h he numbe o conside ed
© The Au ho (s). 2019 Open Access This a icle is dis ibu ed unde he e ms o he C ea i e Commons A ibu ion 4.0
In e na ional License (h p://c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use, dis ibu ion, and
ep oduc ion in any medium, p o ided you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he
C ea i e Commons license, and indica e i changes we e made. The C ea i e Commons Public Domain Dedica ion wai e
(h p://c ea i ecommons.o g/publicdomain/ze o/1.0/) applies o he da a made a ailable in his a icle, unless o he wise s a ed.
Scala e al. BMC Bioin o ma ics (2019) 20:79 Page 2 o 7
expe imen s, especially o use s who a e no amilia
wi h ad anced echniques o da a manipula ion. Some
ools allow he isualiza ion o he en iched Gene On ol-
ogy e ms om mul iple expe imen s [5–7]. Howe e , as
hey a e ypically implemen ed in R, hey equi e a ce -
ain deg ee o p og amming expe ise in o de o p oduce
he desi ed isualiza ions. Mo eo e , since hese me hods
usually o e a s a ic g aphical ou pu , he p oduced plo s
become di icul o ead and in e p e when la ge numbe
o unc ional e ms need o be displayed.
An impo an aspec o some unc ional anno a ions is
he possibili y o de i e a hie a chical s uc u e o hei
base e ms, such as o Kyo o Encyclopedia o Genes and
Genomes (KEGG) pa hways [8], Reac ome pa hways [9]
and Gene On ology e ms [10]. This s uc u e can be used
o o ganize he unc ional e ms and summa ize se s o
ela ed unc ions in supe classes. This ea u e can be
u he exploi ed o educe he dimensionali y o se s o
en iched e ms and o abs ac he unde lying biological
unc ions o highe le els o in e p e a ion.
He e we p esen FunMappOne, an R-shiny use - iendly
so wa e wi h a simple g aphical in e ace ha akes in
inpu lis s o human o mouse genes om mul iple expe i-
men s, op ionally wi h hei gene-associa ed me ics, such
as old change and p- alue. I p o ides unc ionali ies
o s a is ically e alua e o e - ep esen ed biological e ms
om Gene On ology, KEGG, o Reac ome da abases,
g aphically summa ize, and na iga e hem.
Me hod
The h ee-le el hie a chy
In o de o educe he dimensionali y o he se s o
en iched e ms, we in oduced he concep o hie a chical
summa iza ion, ha is he possibili y o explo e en iched
e ms a highe unc ional le els. To do his, a hie a chy is
needed o g oup e ms in supe -classes. By de ini ion, his
s uc u e needs o be ep esen ed as a di ec acyclic g aph,
wi h a oo ca ego y ( ep esen ing he unc ional anno a-
ion) and a se ies o me a- e ms ( eal e ms o unc ional
g oups), de ining p og essi ely specialized g oup o e ms.
This s uc u e is na u ally ound in he in insic o gani-
za ion o KEGG and Reac ome pa hways while i can be
easily de i ed o Gene On ology e ms, as desc ibed in
he nex sec ion. An impo an ac o o he hie a chy
de ini ion and cons uc ion is he numbe o le els o he
hie a chy, namely he dep h o he co esponding g aph
s uc u e: KEGG has an in insic s uc u e based on h ee
le els, while Reac ome pa hways and gene on ology can
ha e mo e han h ee le els ha a e no uni o mly dis-
ibu ed ( he hie a chical chain o me a- e ms can ha e
di e en leng h o di e en e ms). Ha ing many summa-
iza ion le els has he ad an age o making mo e special-
ized g ouping o e ms bu would also complica e he ask
o he use o educe he se dimensionali y and ob ain
easie iews o he en ichmen da a. Fo his eason, we
chose o ollow he KEGG philosophy and homogenize he
h ee hie a chies (KEGG, Reac ome and Gene On ology)
in o de o ha e h ee le els o summa iza ion om he
e ms o he oo . The de ailed implemen a ion o he
hie a chies is desc ibed in he ollowing sec ion.
Hie a chy de ini ion
Figu e 1shows he implemen ed p ocedu e o de ine hie -
a chical s uc u es o KEGG pa hways (panel A), Gene
On ology e ms (panel B) and Reac ome pa hways (panel
C), espec i ely. Fo each anno a ion ype, a h ee-le el
hie a chy was de ined.
•Fo KEGG pa hways (Fig. 1a), he h ee le els o
BRITE unc ional hie a chy was used [8].
•Fo each Gene On ology ca ego y CAT (Biological
P ocesses - BP, Cellula Componen s - CC, and
Molecula Func ions - MF), a h ee-le el hie a chy
was ex ac ed by i s conside ing he g aph
GO_CAT oo ed in CAT (Fig. 1b). Then, he acyclic
di ec ed subg aph GO_CAT_ac was compu ed by
conside ing only he edges ep esen ing he
ela ionship “is_a” o “pa _o ” in GO_CAT. Finally, a
new g aph GO_CAT_hie was buil by conside ing
all he nodes in GO_CAT_ac, and adding, o each
node i, all he edges in he pa h [ i,..., −1]i he
pa h [ i,..., −1,CAT] o leng h a mos 3 al eady
exis ed in GO_CAT_ac. Fo he pa hs
[ i,..., −2, −1,CAT] in GO_CAT_ac o leng h
g ea e han 3, only he a cs o ming he sequence
[ i, −2, −1] we e added o GO_CAT_hie .
•Fo he Reac ome pa hways (Fig. 1C), he se o oo
nodes Rs we e conside ed and a h ee-le el hie a chy
was explica ed. Fi s , he associa ed g aph
REACT_RSi oo ed in CAT was selec ed. Nex , o
each node i he edges [ i, −1,RSi]we e added i he
pa h [ i, −1,RSi]belonged o REACT_RSi.I he
pa h [ i,..., −2, −1,RSi]exis ed in REACT_RSi,
only he edges o ming he sequence [ i, −2,RSi]
we e added o he new g aph ep esen ing he
hie a chy.
FunMappOne algo i hm wo k low
Figu e 2shows he FunMappOne algo i hm wo k low.
The inpu is p o ided as N lis s o genes, one o each
expe imen al condi ion o compa e and, op ionally, N lis s
o modi ica ions (e.g. he old-change o he p- alue) asso-
cia ed wi h each gene. Fo each expe imen analyzed, he
en iched e ms in he chosen unc ional anno a ion a e
compu ed by using he gP o ile R package [4], and a
ma ix Te [NxM] is c ea ed, whe e M is he o al numbe
o en iched e ms. Each elemen Te [i,j] is associa ed wi h
he hype geome ic es p- alue o e m j o he genes
Scala e al. BMC Bioin o ma ics (2019) 20:79 Page 3 o 7
ab c
Fig. 1 De ini ion o he hie a chies. Fo each unc ional anno a ion ype, a model e lec ing he ela ionship be ween unc ional e ms and le els in
hei o iginal s uc u e is shown abo e he co esponding gene a ed hie a chy. Panel a,band c epo hie a chy gene a ion models o KEGG, Gene
On ology and Reac ome, espec i ely. In he second and hi d panel, di e en numbe s indica e di e en unc ional e ms. In panel b,“CAT”canbe
one o he Gene On ology ca ego ies BP, CC o MF
in he i- h lis . Op ionally, Te [i,j] can also be associa ed
wi h a alue ha summa izes he modi ica ion alues (e.g.
he median old change) o he genes om he i- h lis
in e sec ing he gene se o he e m j.
To summa ize he in o ma ion a a highe le el o in e -
p e a ion, a new ma ix Te i[NxK] is c ea ed, whe e i=1,2
is he desi ed heigh o he chosen anno a ion hie a chy
and K is he numbe o di e en e ms a le el i. Each ele-
men Te i[i,j] is hen associa ed wi h a summa y s a ics
(e.g. he median p- alue) o he elemen s Te [i,k] o all
k such ha he e m k is a descendan j in he e e ence
hie a chy.
Finally, gi en a ma ix Te i[NxK] ep esen ing he
en ichmen a le el ias de ined abo e, he possibili y o
eo de and clus e expe imen s, based on a gi en dis-
ance unc ion Dk,l,isimplemen ed.Thisiscompu ed
be ween he ec o s Te i[k,] and Te i[l,] using, al e na-
i ely, a dis ance based on he Jacca d index on he num-
be o common en iched e ms, he Euclidean dis ance
on he alues associa ed wi h e ms, o a combina ion o
hese wo.
In he i s case, he Jacca d index Jk,lis compu ed as
|Te ms(k)∩Te ms(l)|
|Te ms(k)∪Te ms(l)|,whe eTe ms(x)is he se o en iched
e ms o he expe imen xand Dk,lis se as 1 −Jk,l.
In he second case, he se comm(k,l)=Te ms(k)∩
Te ms(l)|is i s conside ed, whe e Te ms(x)is he se o
en iched e ms o he expe imen al condi ion x, heni
|comm(k,l)|≥0 he Euclidean dis ance DEk,lon he sub-
ec o s Te i[k,comm]andTe i[l,comm]iscompu ed.A
combina ion o he wo me hods is implemen ed by c e-
a ing he mean dis ance ma ix Mk=(D+DE01)/2,
whe e Dis hema ixo heJacca dindexandDE01 is he
Euclidean dis ance ma ix scaled in he ange [0,1]. In his
way, he expe imen al condi ions a e clus e ed oge he
no only when hey sha e he same en iched e ms, bu
also conside ing how simila a e he en iched e ms wi h
espec o hei en ichmen p- alue o summa y s a is ic.
A hie a chical clus e ing unc ion is hen applied o he
ma ix using a linkage me hod be ween comple e, single
and wa d.
Resul s and discussion
The analy ical app oach p esen ed abo e was imple-
men ed using R-shiny. The ypical analysis is pe o med
by h ee in e ac ion s eps: i) inpu o gene lis s and modi-
ica ions, ii) g aphical isualiza ion o en iched e ms and
iii) in e ac i e na iga ion o he esul s. A s ep-by-s ep
use manual is a ailable in Addi ional ile 1.
In he i s s ep, he applica ion p o ides a simple g aph-
ical in e ace, whe e he use can submi a sp eadshee
ile wi h he lis s o genes associa ed o each expe imen al
condi ion o in e es and (op ionally) hei modi ica ion
Scala e al. BMC Bioin o ma ics (2019) 20:79 Page 4 o 7
Fig. 2 FunMappOne wo k low. The ool accep s as inpu gene lis s and modi ica ion alues o e e y expe imen al condi ion S1,...,Sn o which
he en ichmen will be ca ied ou . The analysis pe o med on he j- h sample will esul s in a se o en iched e ms Tsj1,...,Tsjk wi h an associa ed
p- alue (En .P) om he en ichmen unc ion applied on he gene lis , o a alue coming om he applica ion o a summa y s a is ic (SS) on he
associa ed modi ica ion alues. A ma ix wi h n ows associa ed o samples and mcolumns associa ed wi h he en iched e ms is hen speci ied o
ep esen he da a s uc u e benea h Le el 3 ep esen a ion o he da a. Ma ices associa ed o highe hie a chical le els a e composed by n ows
and as many columns as he ca ego ies o he le el. Each cell o a highe le el ma ix con ains a alue ob ained by applying SS o he e ms
belonging o he associa ed ca ego y om he Le el 3 ma ix
in o ma ion (e.g. he associa ed old change om a di -
e en ial exp ession analysis). The inpu sp eadshee con-
ains a shee o e e y expe imen al condi ion, named
wi h a condi ion id. In e e y shee , wo columns a e p o-
ided, con aining he gene iden i ie s (En ez Gene, Gene
Symbol, o Ensembl gene ids) and, op ionally, hei mod-
i ica ions, espec i ely. Fu he mo e, an addi ional shee
is equi ed, con aining wo columns wi h he condi ion id
and he condi ion g ouping in o ma ion, espec i ely.
Theuse is henasked ochoose hespecies(human
o mouse), a unc ional anno a ion (Gene On ology - BP,
Gene On ology - CC, Gene On ology - MF, KEGG, Reac-
ome), a summa iza ion unc ion (min, median, mean,
max) o anno a e and summa ize he en iched e ms
wi h p o ided modi ica ions, a p- alue co ec ion me hod
(gSCS [4], bon e oni, d ), and a s a is ical signi icance
h eshold o he en iched unc ional e ms. I he ampli-
ude o gene modi ica ion (e.g. old change, p- alue) is
p o ided, he use selec s whe he he summa ized alue
o he en iched e ms is plo ed in a colo -scale associa ed
o i s alue, o wi h h ee colo s only (nega i e, ze o, posi-
i e); his la e ea u e is use ul when emphasis is gi en o
he dominan sign o he modi ica ion in he e m. Mo e-
o e , i gene modi ica ion alues a e p o ided in he inpu ,
heuse canchoose he ypeo in o ma ion ha willbe
associa ed o he en iched e ms: he e m en ichmen
p- alue, he p o ided modi ica ion alue, o a combina-
ion o e m en ichmen p- alues (En .P) and modi ica ion
alues (MVs), speci ied as MV ×−log(En .P). Al e na-
i ely, i only gene lis s wi hou p o iding modi ica ion
alues a e uploaded, he en ichmen p- alue o each
en iched e m will be displayed.
A e loading he needed iles, a dedica ed panel in he
so wa e g aphical en i onmen shows he con en o he
p o ided ables, along wi h a summa y o each column.
A e clicking he “Gene a e Map” bu on, he ool com-
pu es he en ichmen and shows he “Plo Maps” panel.
A e selec ing he desi ed isualiza ion op ions and click-
ing he “Plo Map” bu on, he ool shows he map o
en iched e ms as a g id (Fig. 3), whe e columns ep esen
expe imen al condi ions, e en ually g ouped based on he
p o ided in o ma ion, and ows ep esen he en iched
e ms g ouped and colo ed based on he co esponding
hie a chy class.
The use can in e ac wi h he gene a ed en ichmen
map in h ee di e en ways: i) by selec ing he le el a
which he map is displayed, ii) by speci ying one o mo e
ca ego ies o e ms o be displayed om a desi ed le el
Scala e al. BMC Bioin o ma ics (2019) 20:79 Page 5 o 7
Fig. 3 In e ac i e Map Visualiza ion. The use can selec he le el o hie a chy o isualize (1) as well as a subse o elemen s o be plo ed a each
le el o hie a chy (2-4). Fu he mo e, he use can selec a subse o he condi ions (5). In he “Plo sec ion” he use can selec o show he ca ego ies
(6) and o keep he aspec a io (7) o he plo . By clicking he bu on “Plo Map” (8) he upda ed map is isualized. A e speci ying he desi ed
heigh (9) and wid h (10) o he pd ha will be downloaded, he use can sa e he image by clicking he “Download” bu on (11). Expe imen s can
be clus e ed by selec ing he numbe o clus e s (12), he desi ed clus e ing unc ion (13), he dis ance unc ion (14), and hen clicking he “Clus e
samples” bu on (15). The map can be ese o he ini ial isualiza ion wi h he p ede ined g ouping by clicking he “Rese clus e ” bu on (16)
o hie a chy, iii) by choosing a subse o expe imen al
condi ions o be plo ed. The selec ion o he summa-
iza ion le el is pe o med ia a d op-down menu. Once
he desi ed le el is selec ed and he “Plo Map” bu -
on is clicked, he panel wi h he esul s is au oma ically
upda ed, p o iding a new map whe e he ows co espond
o he ca ego ies o he chosen le el, g ouped by hei
supe classes in he hie a chy. The colo o he cells in he
new map is associa ed wi h he summa ized alue o all
he en iched e ms in he expe imen al condi ion column
belonging o he ca ego y ow.
The concep o le el ca ego ies can be used o selec
subse s o ows o in e es . This is done by selec ing, o
each ep esen ed le el, he ca ego ies/ e ms o in e es .
The ool subsequen ly upda es he map epo ing only ca -
ego y/ e ms om he selec ed se , hus allowing a mo e
compac iew o he po ion o in e es o he map. Sim-
ila ly, he use can speci y a subse o expe imen s o be
plo ed.
Finally, he columns o he map can be eo de ed by
g ouping expe imen al condi ions ha ing simila en ich-
men p o iles. This is accomplished by selec ing a desi ed
numbe o g oups, a dis ance unc ion among Jac-
ca d, Euclidean and “Jacca d+Euclidean”, and a clus e ing
linkage me hod be ween comple e, single, and wa d. In
he “Clus e ing” sub- ab o “Plo Maps”, FunMappOne
p o ides a isualiza ion o he clus e dend og am as well
as he pa i ioning based on he numbe o desi ed clus-
e s. This unc ionali y can help in selec ing he mos
app op ia e numbe o clus e s o be displayed. Finally,
he cu en iew o he map can be expo ed in a ious
g aphical o ma s.
We inally p o ide a compa ison among FunMappOne
ea u es and hose o e ed by a selec ion o cu en ly a ail-
able ools o unc ional anno a ion ha ing close scope
o FunMappOne. Table 1shows he compa ison o Fun-
MappOne wi h he ollowing gene unc ional analysis
ools: DAVID [1], En ich [2], ToppGene [3], g:p o ile
[4], clus e P o ile [5], Goplo [6]andBACA[7]. As
shown in Table 1, mos o he o he ools o e he pos-
sibili y o analyze KEGG pa hways, Reac ome pa hways
and Gene On ology, also wi h a g aphic ep esen a ion
o he en ichmen esul s. Only Goplo o e s he pos-
sibili y o map gene associa ed alues o e ms, while
En ich and g:p o ile a e he only ools o e ing a web
based g aphical use in e ace. None o he o he ools
o e he possibili y o summa ize esul s and o clus-
e unc ional p o iles om mul iple expe imen s. To

Scala e al. BMC Bioin o ma ics (2019) 20:79 Page 6 o 7
Table 1 Compa ison wi h exis ing ools
Fea u e/Tool DAVID En ich ToppGene g:p o ile clus e P o ile Goplo BACA FunMappOne
KEGG pa hways     
Reac ome pa hways     
Gene On ology      
G aphic ep esen a ion   
G aphic use in e ace   
Hie achycal summa iza ion 
Mul iple expe imen s 
Te m based clus e ing 
Mapping alues on e ms 
Di e en ools a e epo ed on columns, desi ed ea u es a e epo ed on ows. Check-ma ks ep esen he p esence o he ea u e in he ool
ou knowledge, FunMappOne is he only ool p o iding
all o hese unc ionali ies in a use iendly g aphical
in e ace.
Case s udy
We showcase he unc ionali ies o FunMappOne on
a ansc ip ome da ase o mouse hepa ocy es exposed
o 26 chemical compounds wi h di e en ca cinogenic
po en ial [11]. While Schaap e al. de ined he simila i y
be ween he mechanism o ac ion o a pai o chemicals
a he le el o indi idual genes, we es ed he hypo hesis
ha signi ican simila i y pa e ns can be obse ed also a
he unc ional anno a ion le el. An excel ile (Addi ional
ile 2) con aining he o iginally desc ibed lis s o he 30
mos up- egula ed and 30 mos down- egula ed genes in
each compound- o-con ol compa ison, along wi h he
co esponding -s a is ics, was uploaded o FunMappOne.
The anno a ion was pe o med by selec ing he “KEGG”
op ion and “gSCS” as mul iple es ing co ec ion me hod
wi h “0.05” as signi icance h eshold (Addi ional ile 3).
Fo he plo ing, he “median” unc ion was chosen as
summa y s a is ics and colo s we e associa ed o he
summa ized modi ica ion di ec ion o en iched e ms by
selec ing he “sign” op ion (Addi ional ile 3). Chemical
exposu es we e inally o de ed based on he “Jacca d”
dis ance on he numbe o sha ed e ms, and u he clus-
e ed in o 11 g oups using hie a chical clus e ing and
“comple e” agg ega ion me hod.
Addi ional ile 3shows he KEGG en ichmen map a
he le el 1 (Addi ional ile 3A), le el 2 (Addi ional ile 3B),
and a he indi idual pa hway le el 3 (Addi ional ile 3C).
Ou analysis con i med many simila i ies o iginally
desc ibed by Schaap and collabo a o s, such as he one
be ween Wye h-14643 (WY) and Clo ib a e (CF), which
in ou analysis we e g ouped oge he wi h Tac olimus
(FK506) in clus e 11 (Addi ional ile 3C). These chem-
icals modula e PPAR signalling pa hway and a y acid
me abolism ela ed genes, which we obse ed o be
signi ican ly en iched. Mo eo e , we iden i ied a la ge
clus e o compounds (clus e 6) cha ac e ized by no
signi ican ly en iched pa hway, whose pai wise simila i y
o hei mechanism o ac ion we e also desc ibed in he
o iginal epo , bu wi h a low signi icance [11].
In e es ingly, en iched al e a ion o pa hways ela ed
o s e oid ho mone biosyn hesis and chemical ca cino-
genesis was obse ed in a g oup o known ca cinogenic
compounds clus e ed oge he (clus e 5). The isualiza-
ions p oduced a highe le els o he pa hway hie a chy
help he use o immedia ely obse e ha he chemicals in
clus e 5 al e he genes in me abolic pa hways and human
diseases (Addi ional ile 3A). When he isualiza ion a
le el 2 is inspec ed, he no ion ha lipid me abolism
and cance pa hways a e en iched also easily eme ges.
This unc ionali y o FunMappOne becomes e y e ec-
i e when analyzing iche unc ional anno a ions, such as
gene on ology, whe e he numbe o en iched e ms can
be signi ican ly highe (as shown in Addi ional ile 4).
Conclusion
We p esen FunMappOne, a web based s andalone appli-
ca ion ha enables use s o g aphically inspec , na iga e,
and compa e unc ional anno a ions in mul iple expe i-
men s a di e en le els o abs ac ion. This ool acili a es
he analyses o mul iple expe imen al condi ions h ough
a simple use in e ace and dynamic g aphical ep esen a-
ions o he ele an unc ional ca ego ies. The FunMap-
pOne so wa e is open-sou ce and dis ibu ed unde he
AGPL-3 license.
A ailabili y and equi emen s
P ojec name: FunMappOne
P ojec home page: h ps://gi hub.com/G eco-Lab/
FunMappOne
Ope a ing sys em(s): C oss-pla o m
P og amming language: R
O he equi emen s: Shiny
License: AGPL-3
Scala e al. BMC Bioin o ma ics (2019) 20:79 Page 7 o 7
Any es ic ions o use by non-academics: Fo comme -
cial use and modi ica ions please con ac he co espond-
ing au ho .
Addi ional iles
Addi ional ile 1:FunMappOne use manual. Use manual o he
FunMappOne ool. (DOCX 1940 kb)
Addi ional ile 2:Excel ile con aining inpu da a o he case s udy. The
excel ile is composed o one shee o each exposu e and a las shee
con aining g ouping in o ma ion. Each exposu e shee is named wi h he
exposu e ID and con ains wo columns con aining he lis o selec ed
genes and he associa ed -s a is ics, espec i ely. The las shee con ains
wo columns: one epo ing he lis o exposu e IDs and ano he he
co esponding g oup. (XLSX 63 kb)
Addi ional ile 3:Case s udy KEGG en ichmen maps. KEGG en ichmen
maps showing modi ica ion di ec ion a e clus e ing analysis wi h 11
clus e s. Panel A ( op) shows en ichmen esul s summa ized a KEGG Le el
1, panel B (middle) shows en ichmen esul s summa ized a KEGG Le el 2,
panel C (bo om) shows en ichmen esul s summa ized a KEGG Le el 3
(pa hways le el). (PPTX 6869 kb)
Addi ional ile 4:Le el 1,2,3 Reac ome and Gene On ology (BP, CC, MF)
maps o he p oposed case s udy. Reac ome maps ha e been p oduced
by p o iding “Addi ional ile 1” as inpu and choosing “Reac ome”
en ichmen , anno a ion was pe o med using “Bon e oni” as mul iple
es ing co ec ion me hod wi h “0.001” as signi icance h eshold. Th ee
classes o Gene On ology maps ha e been p oduced by p o iding
“Addi ional ile 1” as inpu and choosing “GO” and al e na i ely “BP”, “CC” o
“MF” en ichmen , anno a ion was pe o med using “Bon e oni” as mul iple
es ing co ec ion me hod wi h “0.001” as signi icance h eshold. In bo h
cases, o he plo ing “median” was chosen as summa y s a is ics and map
colo s we e associa ed o he summa ized each e m modi ica ion
di ec ion by choosing he sign op ion. (PDF 3044 kb)
Abb e ia ions
ARO: A oclo 1254; BP: Biological p ocesses; BPA: Bisphenol A; CA: Calyculin A;
CC: Cellula componen s; CF: Clo ib a e; CSA: Cyclospo in A; CSPT: Cispla in; CT:
Ca bon e achlo ide; DEM: Die hyl malea e; DIDP: Diisodecyl ph hala e; DM:
D-manni ol; En .P: Te m en ichmen p- alue; ETP: E oposide; FK506:
Tac olimus; HCE: Hep achlo epoxide; HCH: β-Hexachlo ocyclohexane; KEGG:
Kyo o Encyclopedia o Genes and Genomes; LAC: Lead ace a e; MEN:
Menadione; MF: Molecula unc ions; MMC: Mi omycin C; MNU:
N-Me hyl-N-ni osou ea; MV: Gene modi ica ion alue; OA: Okadaic acid; PB:
Phenoba bi al; SAR: Sodium a seni e; SS: Summa y s a is ics; TBTO: T ibu yl in
oxide; TCE: 1,1,1,-T ichlo oe hane; TCDD: 2,3,7,8-Te achlo odibenzo-p-dioxin;
TCPOBOP: 1,4-Bis[2-(3,5-dichlo opy idyloxy)]benzene; WY: Wye h-14643
Acknowledgemen s
No applicable.
Funding
This s udy was suppo ed by he Academy o Finland (g an ag eemen s
275151 and 292307).
A ailabili y o da a and ma e ials
The FunMappOne ool, i s sou ce code and he example es da a used in his
manusc ip a e a ailable a h ps://gi hub.com/G eco-Lab/FunMappOne.
Au ho s’ con ibu ions
GS and DG concei ed he applica ion and coo dina ed he p ojec . GS, AS and
VSM de eloped he FunMappOne ool. GS, LAS, and DG analyzed and
in e p e ed he esul s o he case s udy. GS, AS, VSM, DG and LAS d a ed he
manusc ip . All au ho s ead and app o ed he inal manusc ip .
E hics app o al and consen o pa icipa e
No applicable.
Consen o publica ion
No applicable.
Compe ing in e es s
The au ho s decla e ha hey ha e no compe ing in e es s.
Publishe ’s No e
Sp inge Na u e emains neu al wi h ega d o ju isdic ional claims in
published maps and ins i u ional a ilia ions.
Au ho de ails
1Facul y o Medicine and Li e Sciences, Uni e si y o Tampe e, A o Ylpön ka u
34 - A o building, FI-33014 Tampe e, Finland. 2BioMediTech Ins i u e,
Uni e si y o Tampe e, A o Ylpön ka u 34 - A o building, FI-33014 Tampe e,
Finland. 3Ins i u e o Bio echnology, Uni e si y o Helsinki, Viikinkaa i 5d,
FI-00014 Helsinki, Finland.
Recei ed: 16 July 2018 Accep ed: 18 Janua y 2019
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